Procainamide Drug Information

• Cardiovascular System: Hypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common with intravenous administration of PA than with intramuscular administration. Because PA is a peripheral vasodilator in concentrations higher than the usual therapeutic range, transient high plasma levels which may occur especially during intravenous administration may produce temporary but at times severe lowering of blood pressure (see OVERDOSAGE and PRECAUTIONS ).
• Multisystem: A lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions (see below) is fairly common after prolonged PA administration, perhaps more often in patients who are slow acetylators (See Boxed Warning and PRECAUTIONS ). While some series have reported less than 1 in 500, others have reported the syndrome in up to 30 percent of patients on long term oral PA therapy. If discontinuation of PA does not reverse the lupoid symptoms, corticosteroid treatment may be effective.
• Hematologic: Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. Agranulocytosis has occurred after repeated use of PA, and deaths have been reported. (See Boxed Warning, WARNINGS section.) Skin: Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rash have also occurred.
• Gastrointestinal System: Anorexia, nausea, vomiting, abdominal pain, diarrhea or bitter taste may occur in 3 to 4 percent of patients taking oral procainamide.
• Nervous System: Dizziness or giddiness, weakness, mental depression and psychosis with hallucinations have been reported.
• Elevated Liver Enzymes: Elevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported. Some patients have had clinical symptoms (e.g., malaise, right upper quadrant pain). Deaths from liver failure have been reported.

Drug Interactions If other antiarrhythmic drugs are being used, additive effects on the heart may occur with PA administration, and dosage reduction may be necessary (see WARNINGS ). Anticholinergic drugs administered concurrently with PA may produce additive antivagal effects on A-V nodal conduction, although this is not as well documented for PA as for quinidine. Patients taking PA who require neuromuscular blocking agents such as succinylcholine may require less than usual doses of the latter, due to PA effects on reducing acetylcholine release.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

• Complete Heart Block: Procainamide should not be administered to patients with complete heart block because of its effects in suppressing nodal or ventricular pacemakers and the hazard of asystole. It may be difficult to recognize complete heart block in patients with ventricular tachycardia, but if significant slowing of ventricular rate occurs during PA treatment without evidence of A-V conduction appearing, PA should be stopped. In cases of second degree A-V block or various types of hemiblock, PA should be avoided or discontinued because of the possibility of increased severity of block, unless the ventricular rate is controlled by an electrical pacemaker.
• Idiosyncratic Hypersensitivity: In patients sensitive to procaine or other ester-type local anesthetics, cross sensitivity to PA is unlikely. However, it should be borne in mind, and PA should not be used if it produces acute allergic dermatitis, asthma, or anaphylactic symptoms.
• Lupus Erythematosus: An established diagnosis of systemic lupus erythematosus is a contraindication to PA therapy, since aggravation of symptoms is highly likely.
• Torsades de Pointes: In the unusual ventricular arrhythmia called "les torsades de pointes" (twistings of the points), characterized by alternation of one or more ventricular premature beats in the directions of the QRS complexes on ECG in persons with prolonged Q-T and often enhanced U waves, Group 1A antiarrhythmic drugs are contraindicated. Administration of PA in such cases may aggravate this special type of ventricular extrasystole or tachycardia instead of suppressing it.

Progressive widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves, as well as increasing A-V block, may be seen with doses which are excessive for a given patient. Increased ventricular extrasystoles, or even ventricular tachycardia or fibrillation may occur. After intravenous administration but seldom after oral therapy, transient high plasma levels of PA may induce hypotension, affecting systolic more than diastolic pressures, especially in hypertensive patients.

Such high levels may also produce central nervous depression, tremor, and even respiratory depression. Plasma levels above 10 mcg/mL are increasingly associated with toxic findings, which are seen occasionally in the 10 to 12 mcg/mL range, more often in the 12 to 15 mcg/mL range, and commonly in patients with plasma levels greater than 15 mcg/mL. Treatment of overdosage or toxic manifestations includes general supportive measures, close observation, monitoring of vital signs and possibly intravenous pressor agents and mechanical cardiorespiratory support. If available, PA and NAPA plasma levels may be helpful in assessing the potential degree of toxicity and response to therapy.

Both PA and NAPA are removed from the circulation by hemodialysis but not peritoneal dialysis. No specific antidote for PA is known.